Mesenchyme () is a type of loosely organized animal embryonic

connective tissue Connective tissue is one of the four primary types of animal tissue, a group of cells that are similar in structure, along with epithelial tissue, muscle tissue, and nervous tissue. It develops mostly from the mesenchyme, derived from the mesod ...

of undifferentiated cells that give rise to most tissues, such as

skin Skin is the layer of usually soft, flexible outer tissue covering the body of a vertebrate animal, with three main functions: protection, regulation, and sensation. Other animal coverings, such as the arthropod exoskeleton, have different ...

blood Blood is a body fluid in the circulatory system of humans and other vertebrates that delivers necessary substances such as nutrients and oxygen to the cells, and transports metabolic waste products away from those same cells. Blood is com ...

, or

bone A bone is a rigid organ that constitutes part of the skeleton in most vertebrate animals. Bones protect the various other organs of the body, produce red and white blood cells, store minerals, provide structure and support for the body, ...

. The interactions between mesenchyme and

epithelium Epithelium or epithelial tissue is a thin, continuous, protective layer of cells with little extracellular matrix. An example is the epidermis, the outermost layer of the skin. Epithelial ( mesothelial) tissues line the outer surfaces of man ...

help to form nearly every

organ Organ and organs may refer to: Biology * Organ (biology), a group of tissues organized to serve a common function * Organ system, a collection of organs that function together to carry out specific functions within the body. Musical instruments ...

in the developing

embryo An embryo ( ) is the initial stage of development for a multicellular organism. In organisms that reproduce sexually, embryonic development is the part of the life cycle that begins just after fertilization of the female egg cell by the male sp ...

Vertebrates

Structure

Mesenchyme is characterized morphologically by a prominent

ground substance Ground substance is an amorphous gel-like substance in the extracellular space of animals that contains all components of the extracellular matrix (ECM) except for fibrous materials such as collagen and elastin. Ground substance is active in the d ...

matrix Matrix (: matrices or matrixes) or MATRIX may refer to: Science and mathematics * Matrix (mathematics), a rectangular array of numbers, symbols or expressions * Matrix (logic), part of a formula in prenex normal form * Matrix (biology), the m ...

containing a loose aggregate of reticular fibers and unspecialized

mesenchymal stem cells Mesenchymal stem cells (MSCs), also known as mesenchymal stromal cells or medicinal signaling cells, are multipotent stromal cells that can differentiate into a variety of cell types, including osteoblasts (bone cells), chondrocytes (cartilage ...

. Mesenchymal cells can migrate easily (in contrast to

epithelial cell Epithelium or epithelial tissue is a thin, continuous, protective layer of Cell (biology), cells with little extracellular matrix. An example is the epidermis, the outermost layer of the skin. Epithelial (Mesothelium, mesothelial) tissues line ...

s, which lack mobility, are organized into closely adherent sheets, and are polarized in an apical- basal orientation).

Development

The mesenchyme originates from the

mesoderm The mesoderm is the middle layer of the three germ layers that develops during gastrulation in the very early development of the embryo of most animals. The outer layer is the ectoderm, and the inner layer is the endoderm.Langman's Medical ...

. From the mesoderm, the mesenchyme appears as an embryologically primitive "soup". This "soup" exists as a combination of the mesenchymal cells plus serous fluid plus the many different tissue proteins. Serous fluid is typically stocked with the many serous elements, such as sodium and chloride. The mesenchyme develops into the tissues of the

lymphatic Lymph () is the fluid that flows through the lymphatic system, a system composed of lymph vessels (channels) and intervening lymph nodes whose function, like the venous system, is to return fluid from the tissues to be recirculated. At the origi ...

and circulatory systems, as well as the musculoskeletal system. This latter system is characterized as

s throughout the body, such as

, and

cartilage Cartilage is a resilient and smooth type of connective tissue. Semi-transparent and non-porous, it is usually covered by a tough and fibrous membrane called perichondrium. In tetrapods, it covers and protects the ends of long bones at the joints ...

. A malignant

cancer Cancer is a group of diseases involving Cell growth#Disorders, abnormal cell growth with the potential to Invasion (cancer), invade or Metastasis, spread to other parts of the body. These contrast with benign tumors, which do not spread. Po ...

of mesenchymal cells is a type of

sarcoma A sarcoma is a rare type of cancer that arises from cells of mesenchymal origin. Originating from mesenchymal cells means that sarcomas are cancers of connective tissues such as bone, cartilage, muscle, fat, or vascular tissues. Sarcom ...

Epithelial to mesenchymal transition

The first emergence of mesenchyme occurs during

gastrulation Gastrulation is the stage in the early embryonic development of most animals, during which the blastula (a single-layered hollow sphere of cells), or in mammals, the blastocyst, is reorganized into a two-layered or three-layered embryo known as ...

from the

epithelial–mesenchymal transition The epithelial–mesenchymal transition (EMT) is a process by which epithelial cells lose their cell polarity and cell–cell adhesion, and gain migratory and invasive properties to become mesenchymal stem cells; these are multipotent stromal ...

(EMT) process. This transition occurs through the loss of epithelial cadherin,

tight junction Tight junctions, also known as occluding junctions or ''zonulae occludentes'' (singular, ''zonula occludens''), are multiprotein Cell junction, junctional complexes between epithelial cells, sealing and preventing leakage of solutes and water. Th ...

s, and

adherens junction In cell biology, adherens junctions (or zonula adherens, intermediate junction, or "belt desmosome") are protein complexes that occur at cell–cell junctions and cell–matrix junctions in epithelial and endothelial tissues, usually more basa ...

s on the

cell membrane The cell membrane (also known as the plasma membrane or cytoplasmic membrane, and historically referred to as the plasmalemma) is a biological membrane that separates and protects the interior of a cell from the outside environment (the extr ...

s of

epithelial cells Epithelium or epithelial tissue is a thin, continuous, protective layer of cells with little extracellular matrix. An example is the epidermis, the outermost layer of the skin. Epithelial ( mesothelial) tissues line the outer surfaces of man ...

. The surface molecules undergo

endocytosis Endocytosis is a cellular process in which Chemical substance, substances are brought into the cell. The material to be internalized is surrounded by an area of cell membrane, which then buds off inside the cell to form a Vesicle (biology and chem ...

and the

microtubule Microtubules are polymers of tubulin that form part of the cytoskeleton and provide structure and shape to eukaryotic cells. Microtubules can be as long as 50 micrometres, as wide as 23 to 27 nanometer, nm and have an inner diameter bet ...

cytoskeleton loses shape, enabling mesenchyme to migrate along the

extracellular matrix In biology, the extracellular matrix (ECM), also called intercellular matrix (ICM), is a network consisting of extracellular macromolecules and minerals, such as collagen, enzymes, glycoproteins and hydroxyapatite that provide structural and bio ...

(ECM). Epithelial–mesenchymal transition occurs in embryonic cells that require migration through or over tissue, and can be followed with a mesenchymal–epithelial transition to produce secondary epithelial tissues. Embryological mesenchymal cells express Protein S100-A4 (''S100A4'') also known as ''fibroblast-specific protein'', which is indicative of their shared properties with the migratory adult

fibroblasts A fibroblast is a type of biological cell typically with a spindle shape that synthesizes the extracellular matrix and collagen, produces the structural framework ( stroma) for animal tissues, and plays a critical role in wound healing. Fibrobla ...

, and c-Fos, an

oncogene An oncogene is a gene that has the potential to cause cancer. In tumor cells, these genes are often mutated, or expressed at high levels.

associated with the down-regulation of epithelial cadherin. Both formation of the

primitive streak The primitive streak is a structure that forms in the early embryo in amniotes. In amphibians, the equivalent structure is the blastopore. During early embryonic development, the embryonic disc becomes oval shaped, and then pear-shaped with the ...

and mesenchymal tissue is dependent on the Wnt/β-catenin pathway. Specific markers of mesenchymal tissue include the additional expression of ECM factors such as

fibronectin Fibronectin is a high- molecular weight (~500-~600 kDa) glycoprotein of the extracellular matrix that binds to membrane-spanning receptor proteins called integrins. Fibronectin also binds to other extracellular matrix proteins such as col ...

and

vitronectin Vitronectin (VTN or VN) is a glycoprotein of the hemopexin family which is synthesized and excreted by the liver, and abundantly found in serum, the extracellular matrix and bone. In humans it is encoded by the ''VTN'' gene. Vitronectin bind ...

Implantation

The first cells of the embryo to undergo EMT and form mesenchyme are the extra-embryonic cells of the

trophectoderm The trophoblast (from Greek : to feed; and : germinator) is the outer layer of cells of the blastocyst. Trophoblasts are present four days after fertilization in humans. They provide nutrients to the embryo and develop into a large part of the pl ...

. These migrate from the body of the

blastocyst The blastocyst is a structure formed in the early embryonic development of mammals. It possesses an inner cell mass (ICM) also known as the ''embryoblast'' which subsequently forms the embryo, and an outer layer of trophoblast cells called the ...

into the

endometrial The endometrium is the inner epithelium, epithelial layer, along with its mucous membrane, of the mammalian uterus. It has a basal layer and a functional layer: the basal layer contains stem cells which regenerate the functional layer. The funct ...

layer of the

uterus The uterus (from Latin ''uterus'', : uteri or uteruses) or womb () is the hollow organ, organ in the reproductive system of most female mammals, including humans, that accommodates the embryonic development, embryonic and prenatal development, f ...

in order to contribute to the formation of the anchored

placenta The placenta (: placentas or placentae) is a temporary embryonic and later fetal organ that begins developing from the blastocyst shortly after implantation. It plays critical roles in facilitating nutrient, gas, and waste exchange between ...

Primary mesenchyme

Primary mesenchyme is the first embryonic mesenchymal tissue to emerge, and it is produced from EMT in

epiblast In amniote embryonic development, the epiblast (also known as the primitive ectoderm) is one of two distinct cell layers arising from the inner cell mass in the mammalian blastocyst, or from the blastula in reptiles and birds. It drives the em ...

cells. In the

, it is induced by the

through Wnt signaling, and produces

endoderm Endoderm is the innermost of the three primary germ layers in the very early embryo. The other two layers are the ectoderm (outside layer) and mesoderm (middle layer). Cells migrating inward along the archenteron form the inner layer of the gastr ...

and

from a transitory tissue called mesendoderm during the process of

. The formation of primary mesenchyme depends on the expression of

WNT3 Proto-oncogene protein Wnt-3 is a protein that in humans is encoded by the ''WNT3'' gene In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA tha ...

. Other deficiencies in signaling pathways, such as in Nodal (a TGF-beta protein), will lead to defective

formation. The tissue layers formed from the primitive streak invaginate together into the embryo and the induced

will ingress and form the

. Mesodermal tissue will continue to differentiate and/or migrate throughout the embryo to ultimately form most

layers of the body.

Neural mesenchyme

Embryological mesenchyme is particularly transitory and soon differentiates after migration. Neural mesenchyme forms soon after primary mesenchyme formation. The interaction with

ectoderm The ectoderm is one of the three primary germ layers formed in early embryonic development. It is the outermost layer, and is superficial to the mesoderm (the middle layer) and endoderm (the innermost layer). It emerges and originates from the o ...

and somite-forming morphogenic factors cause some primary mesenchyme to form neural mesenchyme, or

paraxial mesoderm Paraxial mesoderm, also known as presomitic or somitic mesoderm, is the area of mesoderm in the neurulating embryo that flanks and forms simultaneously with the neural tube. The cells of this region give rise to somites, blocks of tissue running ...

, and contribute to

somite The somites (outdated term: primitive segments) are a set of bilaterally paired blocks of paraxial mesoderm that form in the embryogenesis, embryonic stage of somitogenesis, along the head-to-tail axis in segmentation (biology), segmented animals. ...

formation. Neural mesenchyme soon undergoes a mesenchymal–epithelial transition under the influence of WNT6 produced by

to form

somites The somites (outdated term: primitive segments) are a set of bilaterally paired blocks of paraxial mesoderm that form in the embryonic stage of somitogenesis, along the head-to-tail axis in segmented animals. In vertebrates, somites subdivide in ...

. These structures will undergo a secondary EMT as the

tissue migrates later in development to form structural

such as

and

skeletal muscle Skeletal muscle (commonly referred to as muscle) is one of the three types of vertebrate muscle tissue, the others being cardiac muscle and smooth muscle. They are part of the somatic nervous system, voluntary muscular system and typically are a ...

Neural crest cells The neural crest is a ridge-like structure that is formed transiently between the epidermal ectoderm and neural plate during vertebrate development. Neural crest cells originate from this structure through the epithelial-mesenchymal transition, an ...

(NCCs) form from

neuroectoderm Neuroectoderm (or neural ectoderm or neural tube epithelium) consists of cells derived from the ectoderm. Formation of the neuroectoderm is the first step in the development of the nervous system. The neuroectoderm receives bone morphogenetic pro ...

, instead of the primary mesenchyme, from morphogenic signals of the

neural crest The neural crest is a ridge-like structure that is formed transiently between the epidermal ectoderm and neural plate during vertebrate development. Neural crest cells originate from this structure through the epithelial-mesenchymal transition, ...

. The EMT occurs as a result of Wnt signaling, the influence of

Sox genes ''SOX'' genes (''SRY''-related HMG-box genes) encode a family of transcription factors that bind to the minor groove in DNA, and belong to a super-family of genes characterized by a homology (biology), homologous sequence called the HMG-box (fo ...

and the loss of

E-cadherin Cadherin-1 or Epithelial cadherin (E-cadherin), is a protein that in humans is encoded by the ''CDH1'' gene (not to be confused with the APC/C activator protein CDH1). Mutations are correlated with Hereditary diffuse gastric cancer, gastric, Here ...

from the cell surface. NCCs additionally require the repression of N-cadherin, and neural cell adhesion molecule. NCCs ingress into the embryo from the epithelial neuroectodermal layer and migrate throughout the body in order form multiple

peripheral nervous system The peripheral nervous system (PNS) is one of two components that make up the nervous system of Bilateria, bilateral animals, with the other part being the central nervous system (CNS). The PNS consists of nerves and ganglia, which lie outside t ...

(PNS) cells and

melanocytes Melanocytes are melanin-producing neural crest-derived cells located in the bottom layer (the stratum basale) of the skin's epidermis, the middle layer of the eye (the uvea), the inner ear, vaginal epithelium, meninges, bones, and hea ...

. Migration of NCCs is primarily induced by BMP signaling and its inhibitor, Noggin.

Invertebrates

In some

invertebrate Invertebrates are animals that neither develop nor retain a vertebral column (commonly known as a ''spine'' or ''backbone''), which evolved from the notochord. It is a paraphyletic grouping including all animals excluding the chordata, chordate s ...

s, such as

Porifera Sponges or sea sponges are primarily marine invertebrates of the animal phylum Porifera (; meaning 'pore bearer'), a Basal (phylogenetics) , basal clade and a sister taxon of the Eumetazoa , diploblasts. They are sessility (motility) , sessile ...

Cnidaria Cnidaria ( ) is a phylum under kingdom Animalia containing over 11,000 species of aquatic invertebrates found both in fresh water, freshwater and marine environments (predominantly the latter), including jellyfish, hydroid (zoology), hydroids, ...

Ctenophora Ctenophora (; : ctenophore ) is a phylum of marine invertebrates, commonly known as comb jellies, that inhabit sea waters worldwide. They are notable for the groups of cilia they use for swimming (commonly referred to as "combs"), and they are ...

, and some triploblasts (namely the acoelomates), the term "mesenchyme" refers to a more-or-less solid but loosely organized tissue that consists of a gel matrix (the

mesoglea Mesoglea refers to the extracellular matrix found in cnidarians like coral or jellyfish as well as ctenophores that functions as a hydrostatic skeleton. It is related to but distinct from mesohyl, which generally refers to extracellular material f ...

) with various cellular and fibrous inclusions, located between the

epidermis The epidermis is the outermost of the three layers that comprise the skin, the inner layers being the dermis and Subcutaneous tissue, hypodermis. The epidermal layer provides a barrier to infection from environmental pathogens and regulates the ...

and the

gastrodermis Gastrodermis (from Ancient Greek: , , "stomach"; , , "skin") is the inner layer of Cell (biology), cells that serves as a lining membrane of the gastrovascular cavity in cnidarians. It is distinct from the outer epidermis and the inner dermis and ...

(non-triploblast animals usually are considered to lack "connective" tissue). In some cases, the mesoglea is noncellular. * In

sponge Sponges or sea sponges are primarily marine invertebrates of the animal phylum Porifera (; meaning 'pore bearer'), a basal clade and a sister taxon of the diploblasts. They are sessile filter feeders that are bound to the seabed, and a ...

s, the mesenchyme is called

mesohyl The mesohyl, formerly known as mesenchyme or as mesoglea, is the gelatinous matrix within a sponge. It fills the space between the external pinacoderm and the internal choanoderm. The mesohyl resembles a type of connective tissue and contains ...

. * In diploblasts (Cnidaria and Ctenophora), the mesenchyme is fully ectodermally derived. This kind of mesenchyme is called ectomesodermal, and is not considered true

. * In triploblastic acoelomates (such as

flatworm Platyhelminthes (from the Greek language, Greek πλατύ, ''platy'', meaning "flat" and ἕλμινς (root: ἑλμινθ-), ''helminth-'', meaning "worm") is a Phylum (biology), phylum of relatively simple bilaterian, Segmentation (biology), ...

s), the term

parenchyma upright=1.6, Lung parenchyma showing damage due to large subpleural bullae. Parenchyma () is the bulk of functional substance in an animal organ such as the brain or lungs, or a structure such as a tumour. In zoology, it is the tissue that ...

is sometimes used for the middle (mesenchymal) layer, in which the dense layer includes tissues derived from both ectoderm, and entomesoderm (true mesoderm, derived from entoderm). When cellular material is sparse or densely packed, as in cnidarians, the mesenchyme may sometimes be called collenchyma, or parenchyma in flatworms. When no cellular material is present as in

Hydrozoa Hydrozoa (hydrozoans; from Ancient Greek ('; "water") and ('; "animals")) is a taxonomy (biology), taxonomic class (biology), class of individually very small, predatory animals, some solitary and some colonial, most of which inhabit saline wat ...

, the layer is properly called

. In some colonial cnidarians, the mesenchyme is perforated by gastrovascular channels continuous among colony members. This entire matrix of common basal material is called coenenchyme.

References

* {{Authority control Connective tissue